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Mehta MP , Shapiro WR , Phan SC , Gervais R , Carrie C , Chabot P , Patchell RA , Glantz MJ , Recht L , Langer C , Sur RK , Roa WH , Mahe MA , Fortin A , Nieder C , Meyers CA , Smith JA , Miller RA , Renschler MF
Motexafin gadolinium combined with prompt whole brain radiotherapy prolongs timeto neurologic progression in non-small-cell lung cancer patients with brain metases: results of a phase III trial
International Journal of Radiation Oncology Biology Physics. 2009 Mar;73(4) :1069-1076
PMID: ISI:000264257400017   
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Abstract
Purpose: To determine the efficacy of motexafin gadolinium (MGd) in combination with whole brain radiotherapy (WBRT) for the treatment of brain metastases from non-small-cell lung cancer. Methods and Materials: In an international, randomized, Phase III study, patients with brain metastases from non-small-cell lung cancer were randomized to WBRT with or without MGd. The primary endpoint was the interval to neurologic progression, determined by a centralized Events Review Committee who was unaware of the treatment the patients had received. Results: Of 554 patients, 275 were randomized to WBRT and 279 to WBRT+MGd. Treatment with MGd was well tolerated, and 92% of the intended doses were administered. The most common MGd-related Grade 3+ adverse events included liver function abnormalities (5.5%), asthenia (4.0%), and hypertension (4%). MGd improved the interval to neurologic progression compared with WBRT alone (15 vs. 10 months; p = 0.12, hazard ratio [HR] = 0.78) and the interval to neurocognitive progression (p = 0.057, HR = 0.78). The WBRT patients required more salvage brain surgery or radiosurgery than did the WBRT+MGd patients (54 vs. 25 salvage procedures, p < 0.001). A statistically significant interaction between the geographic region and MGd treatment effect (which was in the prespecified analysis plan) and between treatment delay and MGd treatment effect was found. In North American patients, where treatment was more prompt, a statistically significant prolongation of the interval to neurologic progression, from 8.8 months for WBRT to 24.2 months for WBRT+MGd (p = 0.004, HR = 0.53), and the interval to neurocognitive progression (1) = 0.06, HR = 0.73) were observed. Conclusion: In the intent-to-treat analysis, MGd exhibited a favorable trend in neurologic outcomes. MGd significantly prolonged the interval to neurologic progression in non-small-cell lung cancer patients with brain metastases receiving prompt WBRT. The toxicity was acceptable. (C) 2009 Elsevier Inc.
Notes
Mehta, Minesh P. Shapiro, William R. Phan, See C. Gervais, Radj Carrie, Christian Chabot, Pierre Patchell, Roy A. Glantz, Michael J. Recht, Lawrence Langer, Corey Sur, Ranjan K. Roa, Wilson H. Mahe, Marc A. Fortin, Andre Nieder, Carsten Meyers, Christina A. Smith, Jennifer A. Miller, Richard A. Renschler, Markus F. 19 ELSEVIER SCIENCE INC; 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA 419ZE